Grant: CIHR Fellowship

A continually growing aging population comes with increasing health risks for Canadians. Approximately 750K Canadians are currently living with Alzheimer's disease (AD) or other dementias, and this number is projected to double in 20 years. Current AD research focuses on treatment of patients after development of AD. However, high dimensional neuroimaging will lead to untapped knowledge on disease progression mechanisms of AD, giving us a platform to develop groundbreaking, proactive solutions to AD management. Neuroimaging is critical to better understand the clinical progression of Alzheimer's disease, and understanding processes in the brain and the interplay between pathology and immunology in the onset of AD would better identify: (1) risk factors for AD, (2) therapeutic targets to manage the disease, and (3) understanding of the disease progression mechanisms. The primary aims of this proposal are to understand: (1) what the brain looks like of people with and without AD at a cellular and subcellular level, (2) whether the immune system has a role in disease progression and pathogenesis, and (3) to develop utility of therapeutic targets based on the findings. To answer these questions, we will use multiplexing technologies in order to characterize, phenotype and image the brains of donors. These multiplexing technologies include mass cytometry (CyTOF) and multiplexed ion beam imaging (MIBI), they will allow us to analyze a large number of proteins (>40) in biological samples at the (sub)cellular level. Current technologies are limited in allowing us to only look at 2 or 3 different proteins that we believe have a role in AD; however, CyTOF and MIBI will allow us to look at >40 proteins which have a potential role in AD, and how they interact with one another. This approach will allow us to understand multiple pathways leading to AD pathology, and potentially identify therapeutic targets for the development of novel drugs to manage AD.